This K02 application seeks support which is essential for my continued career development as a newly independent clinical researcher. Funded by a joint NIH Office of Research on Women's Health (ORWH) and NIDA institutional training grant (K12-DA14038; PI: Carolyn Mazure, Program Director: Bruce Rounsaville), I have attained substantial experience in examining sex differences in the association between stress and drug abuse over the past 3 years. I have demonstrated considerable research productivity as evidenced by my peer-reviewed publications, my scientific directorship of a Women's Health Specialized Center of Research (SCOR) on sex, stress and cocaine addiction (P50-DA16556, PI: Sinha), my principal and co-principal investigatorships on two center sections, a previous NIDA funded R01 (R01-DA11077, PI: Sinha) and a recently awarded R01 (AA13892, PI: Sinha). However, this source of salary support (75%) will expire by 12/31/03, leading me to seek an alternative mechanism of funding. Therefore, this K02 award is vital for sustaining my current full-time research focus and for facilitating my development into a fully independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan that fills important gaps in my current expertise in sex-specific factors in the neurobiology of stress and drug relapse. Specifically, I will acquire specialized skills in several additional multidisciplinary areas: (a) basic sex-specific neurobiology of stress and drug addiction; (b) pharmacological and psychological methods to study stress and drug craving states; and (c) advanced bio-statistical tools such as mixed linear models and random effects models. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings on drug abuse and women's health. A representative research project (P50-DA16556, Center Project PI: R. Sinha) is included, which will examine, (1) sex differences in the subjective, autonomic and HPA response to stress and to drug cues as compared to neutral cues in cocaine dependent men and women, and (2) sex differences in the association between early trauma, stressful life events, acute psychobiological responses to stress and to drug cues and cocaine relapse. This research project along with additional lines of research that I am conducting illustrates the significant impact this career award will have in furthering not only my scientific career, but also our fundamental understanding of how stress increases the risk of drug relapse differentially in men and women. Such an understanding will have important implications for the development of gender-specific treatments for cocaine dependence that will ultimately improve the health of cocaine-addicted women and their families.